DV Combined With Toripalimab for Renal Preservation in Solitary Kidney or Renal Insufficiency or Bilateral Multiple UTUC

NCT06354231 | Recruiting Phase 2

• 1 other identifier: RC48-C012
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately 20 participants will be enrolled in the study to evaluate the efficacy and safety of the combination of DV (DV, 2.0 mg/kg, intravenously administered every 2 weeks) and toripalimab (toripalimab, 3.0mg/kg, intravenously administered every 2 weeks). Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy. Efficacy and safety were evaluated by cystoscopy, ureteroscopy, laboratory tests, and imaging examinations after treatment.

Conditions

Renal Insufficiency; Upper Urinary Tract Urothelial Carcinoma; Solitary Kidney

Outcome Measures

Primary Outcomes (1)

• Kidney-intact disease-free survival, KI-DFS

  Defined as the time to systemic relapse or death.

  Up to 12 months

Secondary Outcomes (5)

• Time to progression, TTP

  Up to 3 years

• Time to RNU

  Up to 3 years

• Disease-specific survival time, DSS

  Up to 3 years

• Overall survival

  Up to 3 years

• 3m complete remission

  Up to 3 years

Study Arms (1)

DV+Toripalimab

EXPERIMENTAL

DV, 2.0 mg/kg, intravenously administered every 2 weeks; toripalimab, 3.0mg/kg, intravenously administered every 2 weeks;

Drug: DV; Drug: Toripalimab; Procedure: Laser surgery

Interventions

DV DRUG

2.0 mg/kg, intravenously administered every 2 weeks

Also known as: RC48

DV+Toripalimab

Toripalimab DRUG

3.0mg/kg, intravenously administered every 2 weeks

Also known as: JS001

DV+Toripalimab

Laser surgery PROCEDURE

Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy.

DV+Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old;
• Histologically confirmed isolated renal or renal insufficiency or bilateral upper urinary tract urothelial carcinoma;
• Refusal or ineligibility for RNU;
• Preoperative risk stratification was defined as high-risk UTUC, defined as patients with any of the following factors:
• Hydronephrosis;
• Tumor diameter ≥2cm;
• Urine cytology suggests a high-grade tumor;
• A ureteroscopic biopsy suggests a high-grade tumor;
• CT showed a localized invasion;
• Multifoci diseases;
• With multiple histological subtypes;
• ECOG 0\~1;
• Major organ function is normal (14 days prior to enrollment) if the following criteria are met:
• The blood routine examination criteria should meet (no blood transfusion and no granulocyte colony stimulation agent treatment within 14 days before enrollment): HB≥90 g/L; ANC≥1.5×109 /L; PLT≥100×109 /L;
• Non-functional organic diseases shall meet the following criteria: T-BIL≤1.5×ULN (upper limit of normal value); ALT and AST≤2.5 x ULN; Serum creatinine ≤2×ULN, or endogenous creatinine clearance ≥ 30ml/min(Cockcroft-Gault formula);

You may not qualify if:

• Histopathological examination revealed any small cell component of ureter or pelvis, simple adenocarcinoma, simple squamous cell carcinoma, or simple squamous CIS;
• Previous treatment with other PD-1/PD-L1 inhibitors and/or HER-2 inhibitors;
• Active malignancies other than the disease being studied for treatment (i.e., disease progression within the last 24 months or requiring a change in treatment), only the following special cases are allowed: i. Skin cancer that has been treated within the last 24 months and has been completely cured ii. Adequately treated lobular carcinoma in situ (LCIS) and ductus CIS iii. History of local breast cancer and is receiving antihormonal drugs or history of local prostate cancer (N0M0) and is receiving androgen blocking therapy;
• History of uncontrolled cardiovascular disease, including: 1) any of the following in the past 3 months: unstable angina pectoris, myocardial infarction, ventricular fibrillation, torsion ventricular tachycardia, cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, cerebrovascular accident, or transient ischemic attack; 2) QTc interval prolongation confirmed by ECG evaluation at screening (Fridericia; QTc \> 480 ms); 3) Pulmonary embolism or other venous thromboembolism within the past 2 months;
• Pregnant or lactating women;
• Human immunodeficiency virus (HIV) infection is known unless the subject has been on stable antiretroviral therapy for the past 6 months or longer, has not developed an opportunistic infection in the past 6 months, and has a CD4 count \> 350 in the past 6 months.
• Known history of clinically significant liver disease, including viral hepatitis \[active HBV infection, i.e., HBV DNA positive (\>1×104 copies /mL or \>2000 IU/ml) must be excluded for known hepatitis B virus (HBV) carriers; Known hepatitis C virus infection (HCV) and HCV RNA positive (\>1×103 copies /mL), or other hepatitis, cirrhosis\];
• Have not recovered from the toxic effects of previous anticancer treatment (except for those that are not clinically significant, such as hair loss, skin discoloration, neuropathy, and hearing impairment);
• Delayed wound healing, defined as skin/bedsore ulcers, chronic leg ulcers, known stomach ulcers, or non-healing of incisions;
• Major surgery within 4 weeks before day 1 of Cycle 1 (TURBT is not considered a major surgery);
• Other patients assessed by the investigator as unsuitable for participation in the study.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency; Solitary Kidney

Interventions

toripalimab; Laser Therapy

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urogenital Abnormalities; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Dingwei Ye, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dingwei Ye, Doctor

CONTACT

64175590-82800; dwyeli@163.com

Hailiang Zhang, Doctor

CONTACT

64175590-82800; zhanghl918@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: April 9, 2024
• Study Start: July 20, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)